An NMR study of alanine and glutamate
metabolism in astrocytes and nerve cells (Dr G McBean and Dr J.P.G. Malthouse)
Our interest in the pathways
of glutamate metabolism stems from our observations that a number of gliotoxic
amino acid derivatives (b-N-oxalylamino-L-alanine
and L-alpha-aminoadipate) inhibit the uptake of glutamate into glial
cells, and that at least one of these may block the conversion of glutamate
into glutamine and glutathione in these cells. (McBean, 1994a,b; McBean
et al., 1995). b-N-oxalylamino-L-alanine
has been shown to produce symptoms of Motor Neurone Disease in humans,
and a full understanding of the metabolic interrelationships between neurones
and glial cells is clearly important for determining how these toxins act.
In this study we intend to undertake a detailed examination of the pathways
of alanine utilisation and formation in astrocytes (glial cells), and the
effects of gliotoxins thereon.
Impact of the gliotoxin L-serine-O-sulphate on cellular metabolism in cultured rat astrocytes. Brennan L, Alves PM, Hewage C, Malthouse JP, McBean GJ.Neurochem Int. 2006 Jun;48(8):739-45.
Brennan, L., Hewage,C., Malthouse,J.P.G. and McBean, G.(2004). Gliotoxins disrupt alanine metabolism and glutathione production in C6 glioma cells: a 13C-NMR spectroscopic study. Neurochem International 45, 1155-1165.
Brennan,L., Hewage, C., Malthouse, J.P.G. and McBean, G.J. (2003).
An NMR study of alterations in [1-13C]glucose metabolism in C6 glioma cells by gliotoxic amino acids. Neurochemistry International, 42, 441-448
McBean, G.J. (1994a) Inhibition of the glutamate transporter and glial enzymes in rat striatum by the gliotoxin, aminoadipate. Br. J. Pharmacol. 113, 536-540
McBean, G.J. (1994b) The effect of L-aminoadipate on rat brain g-glutamylcysteine synthetase. Eur. J. Neurosci. 5 (Suppl.6), P159.
McBean, G.J., Doorty, K.B., Tipton,
K.F. and Kollegger, H. (1995) Alteration in the glial cell metabolism of
glutamate by kainate and N-methyl-D-aspartate. Toxicon 33 , 569-576.